Tranexamic acid-loaded starch hemostatic microspheres

Abstract

Efficacious hemostatics have significant potential for use in rapid exsanguinating hemorrhage control by emergency medical technicians or military medics nowadays. Current hemostatics focus primarily on speeding up the formation of blood clots, but inhibiting fibrinolysis is also critical for promoting coagulation and improving survival rates. Here we report a drug-loaded cross-linked microporous starch (TACMS) fabricated by loading tranexamic acid (TA) with antifibrinolytic properties into cross-linked microporous starch (CMS). The results showed that the cross-linking modification improved the mechanical properties and the particle density. The introduction of TA had no influence on water absorption of CMS. TACMS retained good physical hemostatic capacity and excellent biocompatibility. The prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of TACMS with 20 mg g⁻¹ of TA were shortened greatly, indicating the chemical hemostasis of TACMS. TACMS demonstrated a 70% reduction in clotting time in vitro compared to CMS, which effectively inhibited the dissolution of fibrin and increased the strength of blood clots. Importantly, TACMS presented excellent hemostatic performance in rabbit ear artery injury and rabbit liver injury and even better hemostatic ability than Arista®. In conclusion, cross-linking, enzyme hydrolysis and modification of starch greatly improved absorption speed, blood uptake capacity and mechanical strength, and the introduction of TA simultaneously amplified the physical hemostasis and inhibited the dissolution of fibrin. The potent hemostatic ability of TACMS resulted from the synergistic role of physical hemostasis and drug hemostasis. The results of the present study put forward TACMS as a safe and effective hemostatic system and present a platform for further optimization studies of materials with enhanced hemostatic capabilities for specific injury types.